Epidemiology
A 10-study meta-analysis links higher Lp(a) to atrial fibrillation itself, but with very low certainty and extreme heterogeneity (J Clin Med 2025)
Original title: Lipoprotein(a) and Atrial Fibrillation: A Systematic Review and Meta-Analysis
This systematic review and meta-analysis, preregistered in PROSPERO (CRD420251153244) and following PRISMA 2020, searched PubMed/MEDLINE, Embase, Web of Science, Scopus, the Cochrane Library and Google Scholar through September 2025 for observational studies comparing circulating Lp(a) in adults with and without atrial fibrillation (AF). Across 10 studies, Lp(a) was significantly higher in AF patients than controls (pooled mean difference 2.81, 95% CI 1.58-4.05, P < 0.0001), with significant effects in both Asian and European/US subgroups, and sensitivity analyses confirmed the overall effect was stable despite extreme heterogeneity (I2 = 99%). The authors rate the certainty of this evidence as very low by GRADE methodology and call for large, prospective, multi-ethnic studies with standardised biomarker assessment to establish whether Lp(a) causally contributes to AF risk and whether Lp(a)-lowering could modify it.
Original abstract
Background/Objectives: The most prevalent prolonged cardiac arrhythmia and a significant global health burden is atrial fibrillation (AF). Although its connection to AF is still unknown, lipoprotein(a) (Lp(a)), a genetically determined lipoprotein with pro-inflammatory and pro-atherogenic characteristics, has been linked to cardiovascular disease. The purpose of this study was to measure and assess the relationship between circulating Lp(a) levels and AF. Methods: In compliance with the PRISMA 2020 guidelines, a systematic review and meta-analysis were carried out using a protocol that was preregistered in PROSPERO (CRD420251153244). Comprehensive searches of PubMed/MEDLINE, Embase, Web of Science, Scopus, the Cochrane Library, and Google Scholar up until September 2025 were used to find observational studies comparing circulating Lp(a) levels in adults with and without AF. Results: Circulating Lp(a) concentrations were significantly higher in AF patients than in controls across 10 studies (pooled MD = 2.81; 95%CI: 1.58-4.05; p < 0.0001). In the subgroup analysis by geographical setting, studies conducted in Asia and studies from Europe/USA exhibited a statistically significant effect. Despite the extreme heterogeneity (I2 = 99%), sensitivity analyses verified that the overall effect was stable. Conclusions: Our pooled analysis revealed a statistically significant association between Lp(a) and AF; however, the certainty of the evidence was rated as very low according to the GRADE methodology. To elucidate causality, enhance risk stratification, and investigate whether Lp(a)-lowering tactics could alter AF risk, large, prospective, multi-ethnic studies with standardized biomarker assessment are needed.
Summary written by lp-a.org from the published abstract; figures as published. Page updated 17 August 2026. Methods.